The vast majority of patients with hypertrophic cardiomyopathy (HCM) show asymmetric and predominant thickening of the anterior ventricular septum (VS); the posterior left ventricular free wall (PW) is usually spared. In striking contrast, we describe a select group of 17 patients with HCM, with marked asymmetric hypertrophy of PW. Patients were age 13 to 54 years (mean 31); 9 (53%) were female. PW thickness was 20-42 mm, while VS was only 12-24 mm (mean 17); 13 patients had PW thickness which substantially exceeded that of VS, creating the appearance of "inverted" LV asymmetry. Mitral systolic anterior motion and obstruction to LV outflow occurred in 16/17 patients. Most patients (11/17, 65%) had severe cardiac symptoms which did not improve with drug therapy; 6 of these underwent operation (mitral valve replacement in 5, myotomy-myectomy in only 1), and each improved. This subgroup of patients emphasizes the diverse morphologic spectrum of HCM, which includes patients with marked hypertrophy of PW in the presence of only mild VS hypertrophy. Because of relatively modest septal thickening, mitral valve replacement appears to be the operation of choice rather than myotomy-myectomy.